The skin microbiota plays a prominent role in health and disease; however, its contribution to skin tumorigenesis is not well understood. We comparatively assessed the microbial community compositions from excision specimens of the main human non-melanoma skin cancers, actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Keratinocyte skin tumors are characterized by significantly different microbial community compositions, wherein AK and SCC are more similar to each other than to BCC. Notably, in SCC, which represents the advanced tumor entity and frequently develops from AK, overabundance of Staphylococcus aureus, a known skin pathogen, was noted. Moreover, S. aureus overabundance was significantly associated with increased human β-defensin-2 (hBD-2) expression in SCC. By challenging human SCC cell lines with S. aureus, a specific induction of hBD-2 expression and increased tumor cell growth was seen. Increased proliferation was also induced by directly challenging SCC cells with hBD-2. Together, our data indicate that a changed microbial community composition in SCC, specified by S. aureus overabundance, might promote tumor cell growth via modulation of hBD-2 expression.

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Proton pump inhibitors (PPI) are an invaluable therapy option for acid related diseases; however, PPI therapy is also linked to a series of side effects in cirrhosis, such as microbiome alterations, spontaneous bacterial peritonitis and hepatic encephalopathy. Decision tools to balance benefits and risks of PPI therapy are largely missing. In this study, we tested gut-derived biomarkers to identify PPI-associated dysbiosis, its association with gut barrier function and liver-related mortality. In this observational study, faecal microbiome composition data obtained from 16S rDNA sequencing of 90 cirrhotic patients with and without long-term PPI use and additional potential biomarkers identified from the literature were evaluated for their predictive value regarding PPI-associated dysbiosis and liver-related three-year mortality. In addition, faecal calprotectin, faecal zonulin and serum lipopolysaccharides were assessed as markers for intestinal inflammation, gut permeability and bacterial translocation. Streptococcus salivarius , Veillonella parvula and the genus Streptococcus were significantly increased in patients with long-term PPI therapy and performed well as biomarkers for PPI-associated dysbiosis (accuracy: 74%, 72% and 74%, respectively). The abundance of Streptococcus salivarius was linked to intestinal inflammation and gut barrier dysfunction, whereas the abundance of Veillonella parvula showed associations with liver disease severity; both were independent predictors for liver-related three-year mortality. Gut-derived biomarkers of PPI-associated dysbiosis are linked to worse outcome and a potential option to evaluate the risks of adverse events during long-term PPI therapy.

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Irritable bowel syndrome (IBS) is a disorder with brain-gut-microbiome alterations. Gut-directed hypnotherapy (GHT) has been shown to improve quality of life and symptoms in IBS. This therapy targets psychological coping, central nervous processing and brain-gut interaction. Studies have also demonstrated effects of hypnosis on intestinal transit and the mucosal immune system. So far, no study has examined the effect of GHT on the intestinal microbiome. This study aimed at examining microbial composition, IBS symptoms, and psychological distress before and after GHT. Methods: Fecal samples were collected from 38 IBS patients (Rome-III criteria, mean age 44 years, 27 female, 11 male, 22 diarrhea-dominant, 12 alternating-type and 4 constipation-dominant IBS) before and after 10 weekly group sessions of GHT. Assessments in psychological (perceived stress, PSQ; psychological distress, HADS-D; quality of life, visual analogue scales) and IBS symptom-related variables (IBS severity, IBS-SSS; single symptoms, visual analogue scales) were performed with validated questionnaires. Fecal samples underwent microbial 16S rRNA analyses (regions V1–2). Results: Microbial alpha diversity was stable before and after GHT (chao1 2591 ± 548 vs. 2581 ± 539, p = 0.92). No significant differences were found in relative bacterial abundances but trends of reduced abundance of Lachnospiraceae 32.18 (4.14–39.89) Median (Q1–Q3) vs. 28.11 (22.85; 35.55) and Firmicutes: Bacteroidetes ratio after GHT were observable. Significant reductions in symptom severity (323 (266–371) vs. 264 (191–331), p = 0.001) and psychological distress 17.0 (12.6–21.8) vs. 12.0 (8.3–18.0), p = 0.001, and increased well-being were found after GHT. Adequate relief after therapy was reported by 32 (84%) patients. Conclusion: Reductions in IBS symptoms and psychological burden were observed after gut-directed hypnotherapy, but only small changes were found in intestinal microbiota composition. The findings suggest that hypnosis may act by central nervous impact and other factors largely independent from microbiota composition modulating the brain-gut axis, possibly alterations in vagus nerve functioning and microbiota metabolism.